The improvement of current anti-viral vaccines and the development of novel vaccines depends on increasing our understanding of viral attachment and fusion glycoproteins. Critical insight into understanding the antigenic structure of glycoproteins is provided by studying their interaction with monoclonal antibodies (mAbs). For a number of years we have studied the influenza virus hemagglutinin (HA) glycoprotein. This protein serves as a model for other proteins with similar functions (e.g. HIV gp160), and moreover, is important practically in its own right, as influenza still is a major cause of morbidity and mortality both nationally and internationally. Like many viral glycoproteins the HA is a homo-oligomer, consisting of three identical monomeric subunits. In the past year we continued to investigate the interaction of HA with a particular mAb that recognizes an antigenic site that is hidden when the HA trimerizes. We found that this antibody is able to interact with trimers when incubated at body temperature (37 degrees C) or above, and that this reactivity reflects the conformational "breathing" of the tip of the HA, which allows antibody access to a location in the molecule that is inaccessible at lower temperatures. Surprisingly, this "breathing" was restricted by mutations in the HA located near the base of the molecule. These findings indicate that the interaction of viral glycoproteins with protective antibodies can be influenced by very subtle changes in the dynamics of the quaternary structure of the viral protein.